Published online March 2, 2009
PEDIATRICS Vol. 123 No. 3 March 2009, pp. 816-822 (doi:10.1542/peds.2008-0433)
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ARTICLE

Latent Tuberculosis Infection in Children: A Call for Revised Treatment Guidelines

S. Maria E. Finnell, MDa,b,c, John C. Christenson, MDb,c and Stephen M. Downs, MD, MSa,d

a Children's Health Services Research
b Pediatric Infectious Diseases, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana
c Center for International Adoption and Geographic Medicine, Riley Hospital for Children, Indianapolis, Indiana
d Regenstrief Institute for Healthcare, Indianapolis, Indiana

BACKGROUND. Guidelines for latent tuberculosis infection do not consider drug-resistance patterns when recommending treatment for immigrant children.

OBJECTIVES. The purpose of this research was to decide at what rate of isoniazid resistance a different regimen other than isoniazid for 9 months should be considered.

METHODS. We constructed a decision tree by using published data. We studied 3 regimens considered to be effective for susceptible organisms: (1) isoniazid for 9 months, (2) rifampin for 6 months, and (3) isoniazid for 9 months plus rifampin for 6 months. In addition, we evaluated a regimen of isoniazid and rifampin for 3 months. Our base case was a 2-year-old child from Russia with a tuberculin skin test reaction of 12 mm. We assumed a societal perspective and expressed results as cost and cost per case of tuberculosis prevented. We conducted sensitivity analyses to test the stability of our model.

RESULTS. In our baseline analysis, rifampin was the least costly treatment regimen for any child arriving from an area with an isoniazid-resistance rate of ≥11%. Treatment with isoniazid plus rifampin was the most effective but would cost more than $1 million per reactivation case prevented. Isoniazid would become the least costly regimen if any of the following thresholds were met: rifampin resistance given isoniazid resistance of more than 82%; rifampin resistance given no isoniazid resistance of >9%; cost of rifampin more than $47/month; effectiveness of rifampin lower than 63%; effectiveness of isoniazid higher than 74%; and cost of pulmonary tuberculosis less than $7661. Isoniazid and rifampin for 3 months was the least costly for all cases from areas with isoniazid resistance of <80% as long as the regimen's effectiveness was >50% for susceptible bacteria. However, this assumption remains to be proven.

CONCLUSION. Because of the high prevalence of isoniazid resistance, rifampin should be considered for children with latent tuberculosis infection originating from countries with >11% isoniazid resistance.

Key Words: tuberculosis • antibiotic resistance • guideline • child • cost-effectiveness analysis

Abbreviations: LTBI—latent tuberculosis infection • BCG—Bacille Calmette-Guérin • TB—tuberculosis • TST—tuberculin skin test • WHO—World Health Organization • MDR—multidrug resistance

Accepted Jun 17, 2008.


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M. N. Lobato, J. A. Jereb, and K. G. Castro
Do We Have Evidence for Policy Changes in the Treatment of Children With Latent Tuberculosis Infection?
Pediatrics, March 1, 2009; 123(3): 902 - 903.
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